Ibuprofen vs. Continuous Indomethacin in the Treatment of PDA
Information source: Shaare Zedek Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Patent Ductus Arteriosus
Intervention: 1- Continuous indomethacin (Drug); ibuprofen (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Shaare Zedek Medical Center Official(s) and/or principal investigator(s):
Cathy Hammerman, MD, Principal Investigator, Affiliation: Shaare Zedek Medical Center
Summary
The purpose of this study is to determine whether closure of the PDA in premature neonates
using IV ibuprofen vs continuous IV indomethacin has different side effects, eg. effects on
renal function, on blood flow velocity in the superior mesenteric artery, the anterior
cerebral artery, and the renal artery.
Clinical Details
Official title: Comparison of Intravenous Ibuprofen vs. Continuous Indomethacin in the Treatment of Patent Ductus Arteriosus
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacodynamics Study
Primary outcome: To show no differences in urine output and/or in serum creatinine between the treatment groups
Secondary outcome: To show no other clinical differences, eg. NEC, IVH or ROP between the groups; to study doppler flow velocities to these areas; to correlate with BNP levels.
Detailed description:
Despite the fact that ibuprofen appears to minimize the renal side effects seen following
bolus indomethacin, other concerns regarding both short and long-term safety remain.
Indomethacin, on the other hand, has been used to treat premature neonates for many years.
Other than transient vasoconstrictive effects, no significant toxicity has been noted. Thus,
if we were to be able to eliminate the differential renal effects, indomethacin would remain,
for many, the therapy of choice for the premature neonate with a persistent PDA. We
hypothesized that continuous administration of indomethacin would provide this option.
Ibuprofen therapy has not, to date, been compared with indomethacin administered by
continuous infusion. Hence, in the current study we attempted to determine whether continuous
indomethacin administration could potentially offer the same advantages as ibuprofen in
treating PDA, specifically in terms of mitigation of renal side effects. Specifically, our
primary objective was to show no differences in urine output and/or in serum creatinine
between the treatment groups. As a secondary objective, we aimed to show no other potentially
vascular-mediated clinical differences, eg. Necrotizing enterocolitis (NEC), intraventricular
hemorrhage (IVH) or retinopathy of prematurity (ROP) between the groups.
B-type natriuretic peptide (BNP) is released by ventricular myocytes in response to
ventricular volume load. It, in turn, mediates vasodilation, natriuresis and diuresis. Serum
BNP levels have been shown to be clinically useful in differentiating between respiratory and
cardiac disease, in monitoring heart failure therapies and in serving as early diagnostic
biomarkers of ductal patency in premature neonates. As secondary objectives we intend to
determine whether a decrease in BNP levels would be an equally reliable indicator of
therapeutic efficacy in infants treated with ibuprofen as with indomethacin. In addition we
will look at comparative effects on other vascular beds which might mediate long term side
effects described above.
Eligibility
Minimum age: N/A.
Maximum age: 3 Weeks.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- < 1500 gm birth weight with PDA confirmed by echocardiography
Exclusion Criteria:
- Additional congenital heart lesions
- Significant congenital malformations
- Documented infection
- Thrombocytopenia (<60,000)
- IVH grade 4
Locations and Contacts
Additional Information
Starting date: February 2002
Ending date: December 2006
Last updated: June 11, 2007
|
